Expression of p53 as Potential Biomarker in Oral Submucous Fibrosis: An Immunohistochemical Study.

Background: Oral submucous fibrosis (OSMF) is potentially malignant disorder known to transform into oral cancer. The malignant transformation is often associated with changes at the genetic level that in turn is reflected by the altered expression of proteins related to cell cycle, proliferation, and apoptosis. Expression of p53 tumor suppressor gene is one of the common findings in human cancers including the oral cancer. Therefore, the early detection of potentially malignant OSMF has been crucial in the inhibition of oral cancer. Aim and Objectives: To determine the main pathological logical factors and expression of aberrant p53 in OSMF, oral squamous cell carcinomas (OSCC) and in normal patients, to study correlation between p53 expression with clinical staging and histological grading of OSMF. Materials and Methods: An immunohistochemical (IHC) study was performed for p53 expression on 35 cases of OSMF, 10 cases of OSCC with history of habits and 10 normal patients without any habits. Results: The expression of p53 showed a significant difference between normal oral mucosa, OSMF and OSCC samples. Conclusion: The study demonstrated a high incidence of p53 over expression in OSMF and OSCC. The results indicate that p53 over expression may play a role in pathogenesis of OSMF and in the development of Oral squamous cell carcinoma. With early detection of the high-risk patients with OSMF, we can expect to develop more intensive treatment modalities, leading to the reduction in cancer transformation rate from OSMF.

20%-efficient polycrystalline Cd(Se,Te) thin-film solar cells with compositional gradient near the front junction.

Bandgap gradient is a proven approach for improving the open-circuit voltages (VOCs) in Cu(In,Ga)Se2 and Cu(Zn,Sn)Se2 thin-film solar cells, but has not been realized in Cd(Se,Te) thin-film solar cells, a leading thin-film solar cell technology in the photovoltaic market. Here, we demonstrate the realization of a bandgap gradient in Cd(Se,Te) thin-film solar cells by introducing a Cd(O,S,Se,Te) region with the same crystal structure of the absorber near the front junction. The formation of such a region is enabled by incorporating oxygenated CdS and CdSe layers. We show that the introduction of the bandgap gradient reduces the hole density in the front junction region and introduces a small spike in the band alignment between this and the absorber regions, effectively suppressing the nonradiative recombination therein and leading to improved VOCs in Cd(Se,Te) solar cells using commercial SnO2 buffers. A champion device achieves an efficiency of 20.03% with a VOC of 0.863 V.

Expression of Ki67 Biomarker in Oral Submucous Fibrosis with Clinico-Pathological Correlations: A Prospective Study.

OBJECTIVES: Oral Submucous Fibrosis (OSMF) is potentially malignant disorder known to transform into oral cancer. The aim of this study is to determine the degree and pattern of expression of aberrant Ki67 in OSMF, oral squamous cell carcinoma (OSCC) and in normal oral mucosa  patients (NOM). The objective is to correlate between Ki67 expression and degree of dysplasia in OSMF patents and also Ki67 expression with clinical and histological grading of OSMF and OSCC patient. MATERIALS AND METHODS: A prospective cross-sectional study was conducted with purposive sampling technique from Jan 2017 to April 2020.The study groups consist of 35 OSMF cases, 10 cases of each OSCC and NOM. The samples were immunohistochemically analyzed for expression Ki67 antigen using chi-square test (P < 0.05). RESULTS: The expression of Ki67 was significantly higher in OSMF than that of NOM samples, but less than that of OSCC samples. Present study showed correlation between expression of Ki67 with clinical staging and histological grading both in OSMF and OSCC patients. CONCLUSION: The study demonstrated a high incidence of Ki67 over expression in, OSMF and OSCC. Hence, Ki-67 can be widely used as a proliferation marker to measure growth fraction of cells in OSMF and also for determining the severity of epithelial dysplasia.

Expression of Ki67 as potential biomarker in oral submucous fibrosis: An immunohistochemical study.

Background: Oral submucous fibrosis (OSMF) is a potentially malignant disorder (PMD) known to transform into oral cancer. One of the important hallmarks of malignant transformation is the uncontrolled growth rate, commonly reflected as increased cell proliferation which can be significantly detected by proliferative markers such as a high Ki-67 index. Aim: The aim of this study is to evaluate the degree and pattern of expression of Ki67 in OSMF, oral squamous cell carcinoma (OSCC) and in normal mucosal (NOM) patients and to correlate the Ki67 expression with clinical and histological grading of OSMF and OSCC patient. Materials and Methods: A prospective cross-sectional study was conducted over a duration of two years. An immunohistochemical study was performed for Ki76 expression on 35 cases of OSMF, 10 cases of OSCC and 10 normal mucosal patients. Statistical Analysis: Data were analysed using SPSS version 21. Chi-squared test was used to analyse the differences between the intensity levels in OSMF, OSCC and NOM. Results: Expression of Ki67 was significantly higher in OSMF than that of NOM samples but less than that of OSCC samples. Expression of Ki67 increased with increasing grade of clinical and histological stages. Conclusion: The study demonstrated a high incidence of Ki67 overexpression in OSMF and OSCC and showed a correlation between clinical and histological grading of OSMF and OSCC. Identification of high-risk oral PMDs and intervention at premalignant stages could constitute one of the key steps in reducing the mortality, morbidity and cost of treatment associated with malignant transformation of these diseases.

Effects of Cu Precursor on the Performance of Efficient CdTe Solar Cells.

Copper (Cu) incorporation is a key process for fabricating efficient CdTe-based thin-film solar cells and has been used in CdTe-based solar cell module manufacturing. Here, we investigate the effects of different Cu precursors on the performance of CdTe-based thin-film solar cells by incorporating Cu using a metallic Cu source (evaporated Cu) and ionic Cu sources (solution-processed cuprous chloride (CuCl) and copper chloride (CuCl2)). We find that ionic Cu precursors offer much better control in Cu diffusion than the metallic Cu precursor, producing better front junction quality, lower back-barrier heights, and better bulk defect property. Finally, outperforming power conversion efficiencies of 17.2 and 17.5% are obtained for devices with cadmium sulfide and zinc magnesium oxide as the front window layers, respectively, which are among the highest reported CdTe solar cells efficiencies. Our results suggest that an ionic Cu precursor is preferred as the dopant to fabricate efficient CdTe thin-film solar cells and modules.

Investigations on substituted (2-aminothiazol-5-yl)(imidazo[1,2-a]pyridin-3-yl)methanones for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease majorly affecting old age populations. Various factors that affect the progression of the disease include, amyloid plaque formation, neurofibrillary tangles, inflammation, oxidative stress, etc. Herein we report of a new series of substituted (2-aminothiazol-5-yl)(imidazo[1,2-a]pyridin-3-yl)methanones. The designed compounds were synthesized and characterized by spectral data. In vivo anti-inflammatory activity was carried out for screening of anti-inflammatory potential of synthesized compounds. All the compounds were tested for acute inflammatory activity by using carrageenan induced acute inflammation model. Compounds 10b, 10c, and 10o had shown promising acute anti-inflammatory activity and they were further tested for formalin induced chronic inflammation model. Compound 10c showed both acute and chronic anti-inflammatory activity. Compound 10c also showed promising results in AlCl3 induced AD model. Studies on various behavioral parameters suggested improved amnesic performance of compound 10c treated rats. Compound 10c treated rats also exhibited excellent antioxidant and neuroprotective effect with inherent gastrointestinal safety.

An epidemiological study to assess periodontal status among sugar factory workers of Karad taluka using community periodontal index.

OBJECTIVES: Oral health is an integral component of general health. Periodontal disease is one of the most prevalent dental diseases among the population. Researchers have identified an association of various risk factors with periodontal disease. The study aimed to assess the periodontal status among the sugar factory workers of Karad taluka. MATERIALS AND METHODS: The study was conducted among 1200 subjects in the age group of 25-54 years. Personal and sociodemographic data were recorded in the proforma based on the WHO oral health survey form (1997). Periodontal status was assessed using community periodontal index (CPI). For statistical analyses, Chi-square test and Multiple Logistic Regression analyses was performed. RESULTS: The sociodemographic characteristics (age, sex, and socioeconomic status) and deleterious habits like tobacco chewing and smoking were found to be significantly associated with the CPI and LoA scores for the population (P < 0.00001). CONCLUSION: The analysis of the results obtained in this epidemiological study evidenced that periodontitis is prevalent among the sugar factory workers of Karad taluka. There is a need for emphasis on the preventive care.

Performance of Indian diabetic risk score as a screening tool of diabetes among women of industrial urban area.

INTRODUCTION: Hyderabad, the capital hub of Diabetes mellitus type 2 due to the epidemiological transition and varied lifestyle of urbanization. Indian Diabetes Risk Score (IDRS)is used to detect undiagnosed Type 2 diabetes. AIM: This study was taken up with an aim to assess the performance of IDRS as a screening tool to detect undiagnosed cases of type 2 Diabetes mellitus among women in Industrial urban area. SETTING AND DESIGN: A Community based cross sectional study was undertaken at urban field practice area attached to our medical college, Hyderabad. METHODS AND MATERIAL: Women with already diagnosed type 2 Diabetes mellitus and those who were unwilling to give informed consent were excluded from the study. IDRS was used to to detect undiagnosed diabetes. Diabetes was confirmed using blood sugar levels on fasting venous sample. STATISTICAL ANALYSIS USED: Data was entered in Microsoft excel 2010 and was analysed as frequency, Mean+ Standard deviation along with sensitivity and specificity of the test. RESULTS: As per the classification of IDRS 22% were at low risk, 40% medium risk and 38% at high risk. Components of IDRS noted majority about 45.4% with waist circumference > 90cms, no exercise among 66.6% and one parent having diabetes among 26%. Sensitivity was 59.4% and specificity was 37.3% of IDRS with the gold standard test (Fasting blood glucose) to assess the performance. CONCLUSION: IDRS is a cost effective tool which can be used for screening among undiagnosed cases.

Pharmacological investigation of quinoxaline-bisthiazoles as multitarget-directed ligands for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent disease of old age leading to dementia. Complex AD pathogenesis involves multiple factors viz. amyloid plaque formation, neurofibrillary tangles and inflammation. Herein we report of a new series of quinoxaline-bisthiazoles as multitarget-directed ligands (MTDLs) targeting BACE-1 and inflammation concurrently. Virtual screening of a library of novel quinoxaline-bisthiazoles was performed by docking studies. The most active molecules from the docking library were taken up for synthesis and characterized by spectral data. Compounds 8a-8n showed BACE-1 inhibition in micro molar range. One of the compounds, 8n showed BACE-1 inhibition at IC50 of 3 ±â€¯0.07 µM. Rat paw edema inhibition in acute and chronic models of inflammation were obtained at 69 ±â€¯0.45% and 55 ±â€¯0.7%, respectively. Compound 8n also showed noteworthy results in AlCl3 induced AD model. The treated rats exhibited excellent antiamnesic, antiamyloid, antioxidant, and neuroprotective properties. Behavioural parameters suggested improved cognitive functions which further validates the testimony of present study. Moreover, compound 8n was found to have inherent gastrointestinal safety. This new string of quinoxaline-bisthiazoles were identified as effective lead for the generation of potent MTDLs and compound 8n was found to showcase qualities to tackle AD pathogenesis.

Prevalence of oromucosal lesions in relation to tobacco habit among a Western Maharashtra population.

OBJECTIVES: This study was conducted to determine the number and types of oromucosal lesions (OMLs) in relation to tobacco habits in patients who attended the outpatient department. METHODOLOGY: A total of 1730 patients visiting the Department of Oral Medicine and Radiology were interviewed and screened for tobacco habits (smoking and smokeless). Clinical oral examination was conducted with diagnostic instruments using the Color Atlas of Common Oral Diseases as a guide for diagnosis. When clinical features were not diagnostic, a biopsy was done. RESULTS: Of the 1730 outpatients, 975 (56.3% ) individuals used tobacco in one or other forms and 687 (70.4%) of these had OMLs. CONCLUSION: The results of this study provide important information on the prevalence of OMLs in patients seeking dental care. This provides baseline data for future studies on the prevalence of oral lesions in the general population.

Design, synthesis, and evaluation of 4,5,6,7-tetrahydrobenzo[d]thiazole-based novel dual kinase inhibitors of CK2 and GSK3ß.

Casein kinase 2 (CK2) and glycogen synthase kinase-3beta (GSK3ß) are responsible for the phosphorylation of a tumor suppressor protein (PTEN) in a cooperative manner which causes its deactivation. Thus, it is essential to inhibit both kinases simultaneously to prevent PTEN deactivation more efficiently. In this study, we have designed a novel lead from Hit15 which was identified in silico as a dual kinase inhibitor against CK2 and GSK3ß through our previous study. The dataset of structural analogs of the lead was designed and confirmed by pharmacophore mapping and molecular docking. The screened analogs were considered further and a series of "tetrahydrobenzo[d]thiazoles" were synthesized. Compound 1g has shown highest dual kinase inhibitory activity at a concentration of 1.9 µM against CK2 and 0.67 µM against GSK3ß. Our results suggest that the presence of a carboxyl group at the meta position of the phenyl ring plays a vital role in dual kinase inhibition.

Discovery of 2-aminoimidazole and 2-amino imidazolyl-thiazoles as non-xanthine human adenosine A3 receptor antagonists: SAR and molecular modeling studies.

A small-molecule combinatorial library of 24 compounds with 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives was synthesized using a 2-chloro trityl resin. The generated compound library was tested against all the human adenosine receptors subtypes. The 2-aminoimidazole derivatives (6a-6l) showed weak to moderate affinity towards the human adenosine receptors. Further modification to 2-aminoimidazolyl-thiazole derivatives (12a-12l) resulted in an improvement of affinity at adenosine A1, A2A and A3 receptor subtypes. Compound 12b was the most potent and selective non-xanthine human adenosine A3 receptor antagonist of this series. A receptor-based modeling study was performed to explore the possible binding mode of these novel 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives into human adenosine A1, A2A and A3 receptor subtypes.

Thiazolyl-thiadiazines as Beta Site Amyloid Precursor Protein Cleaving Enzyme-1 (BACE-1) Inhibitors and Anti-inflammatory Agents: Multitarget-Directed Ligands for the Efficient Management of Alzheimer's Disease.

Alzheimer's disease (AD) is associated with multiple neuropathological events including ß-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.

Imidazo[1,2-a]pyridines linked with thiazoles/thiophene motif through keto spacer as potential cytotoxic agents and NF-κB inhibitors.

A series of new imidazo[1,2-a]pyridine linked with thiazole/thiophene motif through a keto spacer were synthesized and tested for their cytotoxic potential against three human cancer cell lines including A549, HeLa and U87-MG using MTT assay. Compounds A2, A3, A4, C1 and C2 showed cytotoxicity against all the three cell lines. The selectivity index for compound A4 for A549 and HeLa cells was comparable to that of doxorubicin. Among the synthesized compounds, B5 showed the maximum inhibition of NF-κB activity as ascertained by NF-κB reporter assay (IC50 = 6.5 ±â€¯0.6 µM). Treatment of NCI-H23 cells (EGFR overexpressed, KRAS G12V mutant) with erlotinib and gefitinib along with compounds A4 and B5 indicated synergistic and additive potential of combination therapy.

Development and Validation of a Stability-Indicating HPLC Method for Imidapril and Its Degradation Products Using a Design of Experiment (DoE) Approach.

The present work focused on the application of design of experiment (DoE) principles to the development and optimization of a stability-indicating method (SIM) for the drug imidapril hydrochloride and its degradation products (DPs). The resolution of peaks for the DPs and their drug in a SIM can be influenced by many factors. The factors studied here were pH, gradient time, organic modifier, flow rate, molar concentration of the buffer, and wavelength, with the aid of a Plackett-Burman design. Results from the Plackett-Burman study conspicuously showed influence of two factors, pH and gradient time, on the analyzed response, particularly, the resolution of the closely eluting DPs (DP-5 and DP-6) and the retention time of the last peak. Optimization of the multiresponse processes was achieved through Derringer's desirability function with the assistance of a full factorial design. Separation was achieved using a C18 Phenomenex Luna column (250 × 4.6 mm id, 5 µm particle size) at a flow rate of 0.8 mL/min at 210 nm. The optimized mobile phase composition was ammonium-acetate buffer (pH 5) in pump A and acetonitrile-methanol (in equal ratio) in pump B with a run time of 40 min using a gradient method.

Biomedical Applications of Enzymes From Marine Actinobacteria.

Marine microbial enzyme technologies have progressed significantly in the last few decades for different applications. Among the various microorganisms, marine actinobacterial enzymes have significant active properties, which could allow them to be biocatalysts with tremendous bioactive metabolites. Moreover, marine actinobacteria have been considered as biofactories, since their enzymes fulfill biomedical and industrial needs. In this chapter, the marine actinobacteria and their enzymes' uses in biological activities and biomedical applications are described.

Bioremediation of Industrial Waste Through Enzyme Producing Marine Microorganisms.

Bioremediation process using microorganisms is a kind of nature-friendly and cost-effective clean green technology. Recently, biodegradation of industrial wastes using enzymes from marine microorganisms has been reported worldwide. The prospectus research activity in remediation area would contribute toward the development of advanced bioprocess technology. To minimize industrial wastes, marine enzymes could constitute a novel alternative in terms of waste treatment. Nowadays, the evidence on the mechanisms of bioremediation-related enzymes from marine microorganisms has been extensively studied. This review also will provide information about enzymes from various marine microorganisms and their complexity in the biodegradation of comprehensive range of industrial wastes.

Fuzzy Ce-I(ec, eo) and Fuzzy Completely Ce-I(rc, eo) Functions via Fuzzy e-Open Sets.

We introduced the notions of fuzzy C e-I(ec, eo) functions and fuzzy completely C e-I(rc, eo) functions via fuzzy e-open sets. Some properties and several characterization of these types of functions are investigated.